The examination of the roles of afferent and muscle activity in regulating la afferent-motoneuron (la-MN) synaptic strength will contribute to the long-term goal of understanding synaptic physiology in the adult mammalian central nervous system. The la-MN synapse is a glutamatergic synapse in the spinal cord. Previous studies have shown that blocking action potential activity in a peripheral nerve increases the la-MN synaptic strength of the treated nerve. In these experiments a neurotoxin (TTX), was locally administered to a portion of the sciatic nerve in the hind limb. The toxin eliminated afferent and motor activity in the treated nerve; and resulted in increased la-MN synaptic strength. The specific aims of this research proposal are to elucidate the factors that normally constrain synaptic strength at the la-MN synapse. Specifically, we ask whether the maintenance of impulse-evoked afferent activity can prevent or reduce the increase otherwise observed with TTX treatment alone and whether the maintenance of muscle activity can prevent or reduce the increase in la-MN synaptic strength. These data will provide insight into the factors that regulate synaptic strength in the central nervous system of adult mammals.